3A2O
Crystal Structure of HIV-1 Protease Complexed with KNI-1689
Summary for 3A2O
| Entry DOI | 10.2210/pdb3a2o/pdb |
| Related | 1hpx 1msm 1msn 2zye 3fx5 |
| Related PRD ID | PRD_000584 |
| Descriptor | PROTEASE, GLYCEROL, (4R)-3-[(2S,3S)-3-{[(4-amino-2,6-dimethylphenoxy)acetyl]amino}-2-hydroxy-4-phenylbutanoyl]-5,5-dimethyl-N-(2-methylprop -2-en-1-yl)-1,3-thiazolidine-4-carboxamide, ... (4 entities in total) |
| Functional Keywords | hiv-1 protease, inhibitor, aspartyl protease, hydrolase, protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
| Biological source | Human immunodeficiency virus 1 |
| Total number of polymer chains | 2 |
| Total formula weight | 22142.17 |
| Authors | Adachi, M.,Tamada, T.,Hidaka, K.,Kimura, T.,Kiso, Y.,Kuroki, R. (deposition date: 2009-05-26, release date: 2010-03-02, Last modification date: 2024-05-29) |
| Primary citation | Hidaka, K.,Kimura, T.,Abdel-Rahman, H.M.,Nguyen, J.T.,McDaniel, K.F.,Kohlbrenner, W.E.,Molla, A.,Adachi, M.,Tamada, T.,Kuroki, R.,Katsuki, N.,Tanaka, Y.,Matsumoto, H.,Wang, J.,Hayashi, Y.,Kempf, D.J.,Kiso, Y. Small-sized human immunodeficiency virus type-1 protease inhibitors containing allophenylnorstatine to explore the S2' pocket. J.Med.Chem., 52:7604-7617, 2009 Cited by PubMed Abstract: A series of HIV protease inhibitor based on the allophenylnorstatine structure with various P(2)' moieties were synthesized. Among these analogues, we discovered that a small allyl group would maintain potent enzyme inhibitory activity compared to the o-methylbenzyl moiety in clinical candidate 1 (KNI-764, also known as JE-2147, AG-1776, or SM-319777). Introduction of an anilinic amino group to 2 (KNI-727) improved water-solubility and anti-HIV-1 activity. X-ray crystallographic analysis of 13k (KNI-1689) with a beta-methallyl group at P(2)' position revealed hydrophobic interactions with Ala28, Ile84, and Ile50' similar to that of 1. The presence of an additional methyl group on the allyl group in compound 13k significantly increased anti-HIV activity over 1 while providing a rational drug design for structural minimization and improving membrane permeability. PubMed: 19954246DOI: 10.1021/jm9005115 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (0.88 Å) |
Structure validation
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